As a critical component of our long-term strategy to develop the next generation of leaders in clinical and translational research (CTR), we propose to employ the mentored Career Development Program (KL2) to support full-time post-doctoral, mentored career development as we expand from a “small” to a “medium-sized” hub. In the prior two cycles, we supported career development of an extraordinary group of young clinical and translational scientists, all of whom continue to be engaged in CTR. In the next iteration, our first aim is to continue to provide customized mentoring and didactic content to advance clinical and translational research in our trainee cohort. Our second aim is to challenge KL2 scholars to identify gaps and opportunities relevant to advancing CTR in their fields. We anticipate that providing conceptual and practical tools of improvement science during this early developmental period will have enduring effects on the vision and goals of KL2 graduates. We are confident this strategy will increase the likelihood that our trainees become active agents of transformational change in CTR as they proceed along their career paths. Our third aim is to encourage KL2 scholars to situate their specific research within the full CTR spectrum (T1 to T4) and establish multidisciplinary CTR networks. To enhance networking and team science skills, our KL2 scholars will work in teams to identify nearby scientists and research groups working in each of the CTR stages relevant to their focus. This process will culminate in a capstone effort resulting in a new biennial, multidisciplinary T1–T4 CTR symposium sponsored by the CTSI with invitations to nearby CTSA sites and related institutions. In summary, KL2 scholars will successfully complete training on the responsible conduct of research, general and targeted formal didactics addressing proficiency in CTR, Master’s-level training in multidisciplinary CTR programs, specialized/advanced course work, training in team science, individualized and didactic training in grant preparation, exposure to alternative career opportunities, distance and exchange training, and mentored performance of an innovative high-impact translational research project. Target expectations include first-author publication of ≥3 manuscripts and submission of a K-level grant or equivalent. We will recruit sequential cohorts of four scholars each, all with doctoral degrees (MD, PhD, DDS, PsyD, etc.) and extensive prior research training (≥2 years post-doctorate) plus two investigators meeting identical criteria supported by institutional funds, for 2-year training cycles. Scholars will dedicate ≥75% effort to career development activities supported by KL2 directors with extensive and exemplary mentoring experience. Additional support will include a strongly invested KL2 Executive Committee, a newly constituted Diversity Advisory Committee, and a broad and diverse program faculty who will serve on scholar-specific mentoring commit...